Our stated objective has been to isolate the genes for the human histone H2A family, in particular the H2A.Z gene. The H2A.Z gene has been successfully isolated from both human cDNA and genomic DNA libraries. The homologous gene has also been isolated from bovine and rat cDNA libraries. The DNA of each of these isolates has been subcloned and (partially) sequenced. The DNA sequence of each of the H2A.Z cDNA clones has been shown to encode the H2A.Z polypeptide. Coupled transcription-translation of the H2A.Z cDNA's and analysis of the resultant polypeptide products on a two-dimensional gel electrophoresis system has demonstrated that these cDNA clones are fully representative of the coding sequence of the H2A.Z gene. Genes for the major H2A variant forms, were are actively searching for the gene of the minor H2A variant, H2A.X, in the both human cDNA and genomic DNA libraries. By studying the similarities and differences in the primary DNA structure and genomic organization of the (two) major and (two) minor (basal) histone H2A variant genes we will gain a knowledge of the underlying mechanism(s) of cell cycle dependent and independent regulation of gene expression, and further, what role(s) the basal histone variants might have in the modulation of chromosome structure and function and in the control of cell cycling and proliferation.